Abstract:We investigate the attack of the nitrogen dioxide radical (NO•2) to the guanine—cytosine (GC) base pair and the subsequent tautomeric reactions able to induce mutations, by means of density functional theory (DFT) calculations. The conducted simulations allow us to identify the most reactive sites of the GC base pair. Indeed, the computed relative energies demonstrate that the addition of the NO•2 radical to the C8 position of the guanine base forms to the most stable adduct. Although the initial adducts might… Show more
“…Therefore, autodetachment can effectively compete with the DEA channel of (NIMO − ) # at this energy. We further note that though our calculations for the (NIMO–NO 2 ) fragment predict an appreciable AEA of +2.07 eV, and a DEA threshold of +0.85 eV for the release of NO 2 + (NIMO–NO 2 ) − , we do not observe this simple reaction channel leading to the reactive nitrogen species NO 2 21 .Fig. 2Intensity map of (fragment) anions formed upon electron attachment to nimorazole.…”
While matter is irradiated with highly-energetic particles, it may become chemically modified. Thereby, the reactions of free low-energy electrons (LEEs) formed as secondary particles play an important role. It is unknown to what degree and by which mechanism LEEs contribute to the action of electron-affinic radiosensitisers applied in radiotherapy of hypoxic tumours. Here we show that LEEs effectively cause the reduction of the radiosensitiser nimorazole via associative electron attachment with the cross-section exceeding most of known molecules. This supports the hypothesis that nimorazole is selectively cytotoxic to tumour cells due to reduction of the molecule as prerequisite for accumulation in the cell. In contrast, dissociative electron attachment, commonly believed to be the source of chemical activity of LEEs, represents only a minor reaction channel which is further suppressed upon hydration. Our results show that LEEs may strongly contribute to the radiosensitising effect of nimorazole via associative electron attachment.
“…Therefore, autodetachment can effectively compete with the DEA channel of (NIMO − ) # at this energy. We further note that though our calculations for the (NIMO–NO 2 ) fragment predict an appreciable AEA of +2.07 eV, and a DEA threshold of +0.85 eV for the release of NO 2 + (NIMO–NO 2 ) − , we do not observe this simple reaction channel leading to the reactive nitrogen species NO 2 21 .Fig. 2Intensity map of (fragment) anions formed upon electron attachment to nimorazole.…”
While matter is irradiated with highly-energetic particles, it may become chemically modified. Thereby, the reactions of free low-energy electrons (LEEs) formed as secondary particles play an important role. It is unknown to what degree and by which mechanism LEEs contribute to the action of electron-affinic radiosensitisers applied in radiotherapy of hypoxic tumours. Here we show that LEEs effectively cause the reduction of the radiosensitiser nimorazole via associative electron attachment with the cross-section exceeding most of known molecules. This supports the hypothesis that nimorazole is selectively cytotoxic to tumour cells due to reduction of the molecule as prerequisite for accumulation in the cell. In contrast, dissociative electron attachment, commonly believed to be the source of chemical activity of LEEs, represents only a minor reaction channel which is further suppressed upon hydration. Our results show that LEEs may strongly contribute to the radiosensitising effect of nimorazole via associative electron attachment.
“…Prototropy in heterocompounds was already well-known, when Watson and Crick reported the DNA structure . Taking intramolecular proton-transfer equilibria in nucleobases into account, they proposed an interesting mechanism of point mutations, developed later by other chemists. − In normal DNA, pyrimidine and purine nucleobases take their canonical forms {Figure S1 in Supporting Information (SI)} and interact specifically by formation of H-bonds, i.e., cytosine ( C ) is paired with guanine ( G ), and thymine ( T ) is paired with adenine ( A ). However, in some conditions the canonical forms ( C , G , T , or A ) can be transformed into their rare forms ( C *, G *, T *, or A *), and the natural pairing can be disordered.…”
Intramolecular proton-transfers (prototropic conversions) have been studied for the guanine building block isocytosine (iC), and effects of positive ionization, called one-electron oxidation (iC - e → iC), and negative ionization, called one-electron reduction (iC + e → iC), on tautomeric conversions when proceeding from neutral to ionized isocytosine have been discussed. Although radical cations and radical anions are very short-lived species, the ionization effects could be investigated by quantum-chemical methods. Such kind of studies gives some information about the labile protons and the most basic positions in the neutral and radical forms of the tautomeric system. For investigations, the complete isomeric mixture of isocytosine has been considered and calculations performed in two extreme environments, apolar {DFT(B3LYP)/6-311+G(d,p)} and polar {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. For selected isomers, the G4 theory has also been applied. There are no good relations for energetic parameters of neutral and ionized forms. Ionization energies depend on localization of labile protons. Tautomeric equilibria for neutral and ionized isocytosine, favored sites of protonation and deprotonation, and favored structures of protonated and deprotonated forms strongly depend on environment. Acidity of iC is close to that of the iC conjugate acid, and basicity of iC is close to that of the iC conjugate base. This increase of acid-base properties of charged radicals explains the proton-transfer in ionized pairs of nucleobases. When compared to other pyrimidine bases such as uracil (U) and cytosine (C), which exhibit analogous tautomeric equilibria between nine prototropic tautomers as isocytosine, the tautomeric preferences for iC, iC, iC, U, U, U, C, C, and C are completely different. The differences suggest that acid-base properties of functional groups, their stabilities, and ionization energies play a principal role in proton-transfers for pyrimidine bases and influence compositions of tautomeric mixtures.
“…OOH), [9,10] nitrogen oxide radical (NO . ), [11,12] peroxynitrite (ONOO À ), [13][14][15] etc formed during the normal metabolic activities are deleterious as the products formed during the reactions are implicated in cancer, [16,17] neurodegenerative diseases, [18][19][20] aging, [21] etc. Hence, it is highly desirable to detect the presence of ROS inside living cells.…”
The involvements of in vivo reactive oxygen species, such as superoxide radical (O2.−), peroxynitrite (ONOO−), hydrogen peroxide (H2O2), hydroxyl radical (.OH), peroxyl radical (.OOH), nitrogen oxide radical (NO.), etc in cancer and other diseases are well documented. However, the availability of biosensing elements to detect the presence of reactive oxygen species inside living cells is rare. Herein, B3LYP−D3 dispersion‐corrected density functional theory has been used to design different porous frameworks by coordinating several divalent transition metals, such as Mn+2, Fe+2, Co+2, Cu+2, and Zn+2 with cysteine (Cys) that can detect the presence of various reactive oxygen species. It is found that among all the metals, Cu+2 has the strongest interaction with Cys, thereby producing several stable porous frameworks. Among these frameworks, [Cys‐Cu+2]3(8‐1) is found to possess the largest pore and can adsorb both the anionic (O2.−, ONOO.−) and neutral reactive oxygen species (.OH, .OOH, and NO.) in the aqueous environment. It is thus proposed that the elongation of [Cys‐Cu+2]3(8‐1) framework can generate a novel biosensing element, which can be used for the sensing of various reactive oxygen species. However, experimental verification of the proposed material is required to confirm its applicability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
